Interleukin-25 (IL-25) is a cytokine that is structurally related to interleukin-17 (IL-17) and is sometimes referred to as IL-17E. It is a secreted, homodimeric glycoprotein that interacts with and signals through the heterodimeric IL-17RB/IL-17RA receptor (Iwakura, et. al., (2010), Immunity, 34:149). IL-25 is produced by Th2 cells, epithelial cells, endothelial cells, alveolar macrophages, mast cells, eosinophils and basophils (Rouvier, E. et. al., (1993), J. Immunol. 150:5445-5456; Pan, G. et. al., (2001), J. Immunol. 167:6559-6567; Kim, M. et. al., (2002), Blood 100:2330-2340). Signaling through IL-25 is associated with eosinophil recruitment, initiation of Th2 and Th9 responses and suppression of Th1 and Th17 cell responses. IL-25 induces the production of other cytokines, including IL-4, IL-5 and IL-13, in multiple tissues (Fort, M M et. al., (2001), Immunity 15:985-995).
IL-25 has been implicated in chronic inflammation associated with the gastrointestinal tract and the IL-25 gene has been identified in a chromosomal region associated with autoimmune diseases of the gut, such as inflammatory bowel disease (IBD) (Büning, C. et. al., (2003), Eur. J. Immunogenet. October; 30(5): 329-333). IL-25 has also been shown to be upregulated in samples from patients with asthma (Sherkat, R. et. al., (2014), Asia Pac. Allergy October; 4(4):212-221). Accordingly, blockade of IL-25 signaling may be useful for the treatment of various disorders associated with IL-25 activity or expression.
Anti-IL-25 antibodies are mentioned, e.g., in U.S. Pat. Nos. 8,785,605; 8,658,169 and 8,206,717; and PCT publications WO2011/123507; WO2010/038155 and WO2008/129263. Nonetheless, there is a need in the art for novel IL-25 antagonists, such as the anti-IL-25 antibodies of the present invention, for the treatment of diseases or disorders associated with IL-25 expression and/or signaling, or other conditions associated with IL-25 expression and/or signaling.